Dissociative ionization and Coulomb explosion of CH4 in two-color asymmetric intense laser fields.

Directional fragment ejection from a tetrahedral molecule CH4 in linearly polarized two-color (ω and 2ω) asymmetric intense laser fields (50 fs, 1.4 × 1014 W cm-2, 800 nm and 400 nm) has been studied by three-dimensional ion coincidence momentum imaging. The H+ fragment produced from dissociative ionization, CH4 → H+ + CH3 + e-, is preferentially ejected on the larger amplitude side of the laser electric fields. Comparison with theoretical predictions by weak-field asymptotic theory shows that the observed asymmetry can be understood by the orientation selective tunneling ionization from the triply degenerated highest occupied molecular orbital (1t2) of CH4. A similar directional ejection of H+ was also observed for the low kinetic energy components of the two-body Coulomb explosion, CH4 → H+ + CH3+ + 2e-. On the other hand, the fragment ejection in the opposite direction were observed for the high energy component, as well as H2+ produced from the Coulomb explosion CH4 → H2+ + CH2+ + 2e-. Possible origins of the characteristic fragmentation are discussed.

Helicity-dependent dissociative tunneling ionization of CF4 in multicycle circularly polarized intense laser fields.

Dissociative tunneling ionization of tetrafluoromethane (CF4) in circularly polarized ultrashort intense laser fields (35 fs, 0.8 × 1014 W cm-2, 1035 nm), CF4 → CF4+ + e- → CF3+ + F + e-, has been studied by three-dimensional electron-ion coincidence momentum imaging. The photoelectron angular distribution in the recoil frame revealed that the dissociative tunneling ionization occurs efficiently when the laser electric field points from F to C. The obtained results are qualitatively consistent with the theoretical predictions by the weak-field asymptotic theory (WFAT) for tunneling ionization from the highest and next-highest occupied molecular orbitals, HOMO (1t1), and HOMO-1 (4t2), respectively. On the other hand, the angular distribution shows clear dependences on the polarization helicity, indicating that the breaking of the C-F bonds is sensitive to the helicity of the multicycle circularly polarized laser fields.

Interaction of Amyloid-ß-(1-42) Peptide and Its Aggregates with Lipid/Water Interfaces Probed by Vibrational Sum-Frequency Generation Spectroscopy.

In this study, we use surface-sensitive vibrational sum-frequency generation (VSFG) spectroscopy to investigate the interaction between model lipid monolayers and Aß(1-42) in its monomeric and aggregated states. Combining VSFG with atomic force microscopy (AFM) and thioflavin T (ThT) fluorescence measurements, we found that only small aggregates with probably a ß-hairpin-like structure adsorbed to the zwitterionic lipid monolayer (DOPC). In contrast, larger aggregates with an extended ß-sheet structure adsorbed to a negatively charged lipid monolayer (DOPG). The adsorption of small, initially formed aggregates strongly destabilized both monolayers, but only the DOPC monolayer was completely disrupted. We showed that the intensity of the amide-II' band in achiral (SSP) and chiral (SPP) polarization combinations increased in time when Aß(1-42) aggregates accumulated at the DOPG monolayer. Nevertheless, almost no adsorption of preformed mature fibrils to DOPG monolayers was detected. By performing spectral VSFG calculations, we revealed a clear correlation between the amide-II' signal and the degree of amyloid aggregates (e.g., oligomers or (proto)fibrils) of various Aß(1-42) structures. The calculations showed that only structures with a significant amyloid ß-sheet content have a strong amide-II' intensity, in line with previous Raman studies. The combination of the presented results substantiates the amide-II(') band as a legitimate amyloid marker.

Why whales are big but not bigger: Physiological drivers and ecological limits in the age of ocean giants.

The largest animals are marine filter feeders, but the underlying mechanism of their large size remains unexplained. We measured feeding performance and prey quality to demonstrate how whale gigantism is driven by the interplay of prey abundance and harvesting mechanisms that increase prey capture rates and energy intake. The foraging efficiency of toothed whales that feed on single prey is constrained by the abundance of large prey, whereas filter-feeding baleen whales seasonally exploit vast swarms of small prey at high efficiencies. Given temporally and spatially aggregated prey, filter feeding provides an evolutionary pathway to extremes in body size that are not available to lineages that must feed on one prey at a time. Maximum size in filter feeders is likely constrained by prey availability across space and time.

Human pregnancy is accompanied by modifications in B cell development and immunoglobulin profile.

Though human pregnancy success has been classically linked with a shift into a Th2 immunoglobulin producing cell response, a clear picture concerning B cell development and immunoglobulin profile during human pregnancy is missing. We analyzed in this work the dynamic of different B cell populations in peripheral blood of pregnant women on the first, second and third trimester of pregnancy. As control, age-matched non-pregnant fertile women were included. Additionally, we quantified the levels of immunoglobulin (IgG1, IgG2, IgG3, IgG4, IgM, IgA and IgE) in the serum of pregnant and non-pregnant women. We observed a significant decrease in the percentages of transitional B cells in peripheral blood of pregnant women as compared to non-pregnant control women. Besides, percentages of naïve as well as switched and non-switched memory B cells in peripheral blood of pregnant women were similar to those in non-pregnant control women. Interestingly, although we did not observe differences in the activation status of B cells as well as in the percentages of plasma cells between pregnant and non-pregnant women, we observed significantly higher levels of IgM, IgA, IgG3, more likely natural antibodies, as well IgG4 in serum of pregnant women compared to non-pregnant age matched control women.

Click communication in wild harbour porpoises (Phocoena phocoena).

Social delphinids employ a vocal repertoire of clicks for echolocation and whistles for communication. Conversely, the less social and acoustically cryptic harbour porpoises (Phocoena phocoena) only produce narrow-band high-frequency (NBHF) clicks with properties that appear poorly suited for communication. Nevertheless, these small odontocetes likely mediate social interactions, such as mate choice and mother-calf contact, with sound. Here, we deployed six tags (DTAG3) on wild porpoises in Danish waters for a total of 96 hours to investigate if the patterns and use of stereotyped NBHF click trains are consistent with a communication function. We show that wild porpoises produce frequent (up to 27 • min-1), high-repetition rate click series with repetition rates and output levels different from those of foraging buzzes. These sounds are produced in bouts and frequently co-occur with emission of similar sounds by nearby conspecifics, audible on the tags for >10% of the time. These results suggest that social interactions are more important to this species than their limited social encounters at the surface may indicate and that these interactions are mediated by at least two broad categories of calls composed of short, high-repetition rate click trains that may encode information via the repetition rate of their stereotyped NBHF clicks.

Protonation of aqueous alanine by photoionization of water.

Hydronium ions produced by photolysis of water are used to study the protonation dynamics of alanine zwitterions in water. The measurements are done by UV-VIS and UV-IR femtosecond transient absorption spectroscopy on alanine in H2O and D2O. It is estimated that the reaction rate constant for the deuteration of alanine zwitterions is 4 × 1010 M-1 s-1, while the reverse process has a rate constant of 2 × 108 s-1. In addition to hydronium ions the photolysis of water yields hydrogen atoms and hydrated electrons together with hydroxyl radicals and hydroxyl ions. However, no other products resulting from reactions between aqueous alanine and the photolysis products of water are positively identified during the first 530 ps after the photolysis. Potential secondary reactions that are not observed experimentally are discussed and an upper limit is set for their yield where possible.

Progesterone and estradiol exert an inhibitory effect on the production of anti-inflammatory cytokine IL-10 by activated MZ B cells.

The main message of this work is the fact that female sex hormones, progesterone and estradiol, whose levels significantly rise during pregnancy, inhibit the production of anti-inflammatory cytokine IL-10 with no apparent effect on pro-inflammatory cytokine TNF-α by activated MZ B cells. This is an important piece of information and helps to better understand how the maternal immune system controls the balance between immune tolerance and immune activation during pregnancy leading to the simultaneously acceptance of the semi-allogeneic fetus and the proper defense of the mother against pathogens during this critical period of time.

Expression analysis of cannabinoid receptors 1 and 2 in B cells during pregnancy and their role on cytokine production.

The endocannabinoid system consists in a family of lipids that binds to and activates cannabinoid receptors. There are two receptors so far described, the cannabinoid receptor 1 (CB1) and 2 (CB2). In the context of pregnancy, the endocannabinoid system was shown participates in different key aspects of reproductive events. B-lymphocytes are pleiotropic cells belonging to the adaptive arm of the immune system. Besides immunoglobulin production, B-lymphocytes were recently shown to be actively involved in antigen presentation as well as cytokine production, thus playing a central role in immunity. In this study we first aimed to characterize the expression of CB1 and CB2 receptors in B cells during pregnancy and then analyze the impact of their activation in term of cytokine production by B cells from pregnant and non-pregnant mice. We observed that the expression of CB1 and CB2 receptors in B-lymphocytes is differentially regulated during pregnancy. While CB2 expression is down regulated CB1 is augmented in B-lymphocytes of pregnant mice. Additionally, the treatment of activated B-lymphocytes with specific CB1 and CB2 agonists, showed a different response in term of cytokine production. Particularly, CB1 against boosted the production of the anti-inflammatory cytokine IL-10 by activated B-lymphocytes from pregnant mice.

Measurement and laser control of attosecond charge migration in ionized iodoacetylene.

The ultrafast motion of electrons and holes after light-matter interaction is fundamental to a broad range of chemical and biophysical processes. We advanced high-harmonic spectroscopy to resolve spatially and temporally the migration of an electron hole immediately after ionization of iodoacetylene while simultaneously demonstrating extensive control over the process. A multidimensional approach, based on the measurement and accurate theoretical description of both even and odd harmonic orders, enabled us to reconstruct both quantum amplitudes and phases of the electronic states with a resolution of ~100 attoseconds. We separately reconstructed quasi-field-free and laser-controlled charge migration as a function of the spatial orientation of the molecule and determined the shape of the hole created by ionization. Our technique opens the prospect of laser control over electronic primary processes.

Observation of laser-induced electronic structure in oriented polyatomic molecules.

All attosecond time-resolved measurements have so far relied on the use of intense near-infrared laser pulses. In particular, attosecond streaking, laser-induced electron diffraction and high-harmonic generation all make use of non-perturbative light-matter interactions. Remarkably, the effect of the strong laser field on the studied sample has often been neglected in previous studies. Here we use high-harmonic spectroscopy to measure laser-induced modifications of the electronic structure of molecules. We study high-harmonic spectra of spatially oriented CH3F and CH3Br as generic examples of polar polyatomic molecules. We accurately measure intensity ratios of even and odd-harmonic orders, and of the emission from aligned and unaligned molecules. We show that these robust observables reveal a substantial modification of the molecular electronic structure by the external laser field. Our insights offer new challenges and opportunities for a range of emerging strong-field attosecond spectroscopies.

Strain Elastography for Prediction of Malignancy in Soft Tissue Tumours--Preliminary Results.

PURPOSE: To evaluate the ability of strain elastography to predict malignancy in patients with soft tissue tumors, and to compare three evaluation methods of strain elastography: strain ratios, strain histograms and visual scoring. MATERIALS AND METHODS: 60 patients with 61 tumors were analyzed in the study. All patients were referred due to suspicion of malignant soft tissue tumors after diagnostic imaging (contrast-enhanced MRI, CT or PET-CT). Ultrasound-guided biopsy was preceded by the recording of strain elastography video clips, which were evaluated in consensus between three investigators. Strain ratio, strain histogram analysis and visual scoring using a five-point visual scale were compared with the final pathology from either biopsy or resection of the tumors. RESULTS: The difference between the mean strain ratio for malignant and benign tumors was significant (p = 0.043). The mean strain ratios for malignant and benign tumors were 1.94 (95% CI [0.37; 10.21]) and 1.35 (95% CI [0.32; 5.63]), respectively. There were no significant differences for strain histograms or visual scoring. Liposarcomas had lower mean strain ratio, strain histogram values, and visual scoring than other malignant tumors. When analyzing a subgroup of patients without fat-containing tumors (n = 46), based on appearance on MRI or CT, the difference between the mean strain ratios for malignant and benign tumors increased (p = 0.014). CONCLUSION: The mean strain ratios of malignant tumors were significantly higher than the mean strain ratios of benign tumors. There was no significant difference for strain histograms and visual scoring. Strain ratios may be used as an adjunct in soft tissue tumor diagnosis, possibly minimizing the number of biopsies.

Hemorragia digestiva alta por várices gástricas secundarias a trombosis de vena esplénica tratada con esplenectomía / Upper gastrointestinal bleeding due to gastric varices secondary to splenic vein thrombosis treated by splenectomy

Upper gastrointestinal bleeding secondary to acute variceal hemorrhage is a medical emergency, with significant morbidity and mortality, which usually requires a multidisciplinary approach from gastroenterologists, intensive care physicians, and surgeons. The most common cause of variceal bleeding is the one that arises from portal hypertension associated with cirrhosis, and best described in terms of prevention, initial management and following treatment that in the minority of cases can be definitive without complex interventions, including liver transplant in cirrhotic patients. Within the etiologies not arising from portal hypertension, splenic vein thrombosis is one of the most important. Characterized by an endoscopic appearance of fundal or isolated gastric varices, without esophageal involvement, a variable number of cases manifest clinically as variceal hemorrhage. Based on different pathophysiology compared to esophageal varices, response to initial treatment is different, endoscopic management involve the use of adhesives (e.g. cyanoacrylate) as treatment of choice, and, in selected cases, surgical treatment can provide a definitive solution. Here we present a clinical case of an adult patient, without history of cirrhosis, who presented to the emergency department with severe upper gastrointestinal bleeding secondary to gastric varices, admitted in Intensive Care Unit and treated with endoscopy. Complementary studies with abdominal CT showed spleen vein thrombosis, enlarged spleen and multiple varicesin gastric body and fundus. After stabilization, splenectomy was performed as definitive treatment, with regression of gastric varices on ambulatory control with an upper endoscopy...

La hemorragia digestiva alta por sangrado variceal agudo constituye una emergencia médica, con morbimortalidad significativa asociada, requiriendo manejo multidisciplinario de gastroenterólogos, intensivistas y cirujanos. El sangrado variceal por hipertensión portal secundario a daño hepático crónico es el más habitual y mejor caracterizado en prevención, enfrentamiento inicial y manejo posterior, que en la minoría de los casos puede ser definitivo, sin intervenciones complejas, incluyendo trasplante hepático en pacientes cirróticos. Dentro de las causas de sangrado variceal no asociadas a hipertensión portal, la trombosis de vena esplénica es una de las principales. Caracterizada por presentarse en endoscopia como várices gástricas fúndicas o aisladas sin compromiso esofágico, se manifiestan clínicamente como sangrado variceal agudo en un porcentaje variable de casos. Por tener etiopatogenia distinta a las várices por hipertensión portal, la respuesta frente a las medidas terapéuticas iniciales es distinta, el tratamiento endoscópico de elección es el uso de adhesivos tipo cianoacrilato, y en casos seleccionados, el enfrentamiento quirúrgico puede ofrecer una solución definitiva. Presentamos el caso de una paciente sin antecedentes de daño hepático crónico, que se presentó con hemorragia digestiva alta por sangrado de várices gástricas, con manejo inicial en unidad de paciente crítico y hemostasia por vía endoscópica. En estudio complementario se objetivó trombosis de la vena esplénica con esplenomegalia y múltiples formaciones varicosas en fondo y cuerpo gástrico. Posterior a estabilización se realizó esplenectomía como manejo definitivo, logrando regresión de várices gástricas en endoscopia de control...

Nitric oxide improves the hemodynamic performance of the hypoxic goldfish (Carassius auratus) heart.

Goldfish tolerate prolonged and severe hypoxia, thus representing a well-suited model to study the maintenance of cardiac function when O(2) availability represents a limiting factor. Using a working heart preparation, we explored the role of the intracardiac nitric oxide synthase (NOS)-derived nitric oxide (NO) under normoxic and hypoxic conditions. Cardiac performance was examined both under basal (constant preload and afterload) and loading conditions, i.e. preload-induced increases in stroke volume (SV) and hence cardiac output at constant afterload (the Frank-Starling response). Hypoxic hearts showed an increased basal mechanical performance compared to the normoxic counterpart. Under basal conditions, in both normoxic and hypoxic hearts, NOS and soluble guanylyl cyclase (sGC) inhibition increased SV, while exogenous NO supply decreased it. The normoxic heart was very sensitive to filling pressure increases; the maximum SV = 1.08 ± 0.09 mL/kg body mass was obtained at 0.4 kPa. Acute hypoxia increased this sensitivity, SV reaching the maximum value (1.45 ± 0.12 mL/kg body mass) at 0.25 kPa. NOS inhibition by L-NMMA reduced the Frank-Starling response under normoxia, but was ineffective under acute hypoxia, where NO may come from nitrite reduction. In both conditions, sGC inhibition induced a reduction of the cardiac response to preload. Moreover, under acute hypoxia, NO scavenging significantly reduced the Frank-Starling response. The hypoxia-induced hemodynamic patterns were complemented by Western blotting analysis which revealed increased expressions of NOS and hypoxia inducible factor α(HIF-1α). In conclusion, we demonstrated that intracardiac NO/NOS enhances goldfish heart performance, remarkably expanding its hypoxic tolerance.

Proton pump inhibitor use may not prevent high-grade dysplasia and oesophageal adenocarcinoma in Barrett's oesophagus: a nationwide study of 9883 patients.

BACKGROUND: Proton pump inhibitors (PPI) may potentially modify and decrease the risk for development of oesophageal adenocarcinoma in Barrett's oesophagus (BO). AIM: To investigate if the intensity and adherence of PPI use among all patients with BO in Denmark affected the risk of oesophageal adenocarcinoma. METHODS: We performed a nationwide case-control study in Denmark among 9883 patients with a new diagnosis of BO. All incident oesophageal adenocarcinomas and high-grade dysplasias were identified, and risk ratios were estimated on the basis of prior use of PPIs. Sex- and age-matched BO patients without dysplasia or malignancies in a 10:1 ratio were used for comparison. Conditional logistic regression was used for analysis, adjusting for low-grade dysplasia, gender and medication. RESULTS: We identified 140 cases with incident oesophageal adenocarcinomas and/or high-grade dysplasia, with a median follow-up time of 10.2 years. The relative risk of oesophageal adenocarcinoma or high-grade dysplasia was 2.2 (0.7-6.7) and 3.4 (95% CI: 1.1-10.5) in long-term low- and high-adherence PPI users respectively. CONCLUSIONS: No cancer-protective effects from PPI's were seen. In fact, high-adherence and long-term use of PPI were associated with a significantly increased risk of adenocarcinoma or high-grade dysplasia. This could partly be due to confounding by indication or a true negative effect from PPIs. Until the results from future studies hopefully can elucidate the association further, continuous PPI therapy should be directed at symptom control and additional modalities considered as aid or replacement.

Decay rate measurement of the first vibrationally excited state of MgH+ in a cryogenic Paul trap.

We present a method to measure the decay rate of the first excited vibrational state of polar molecular ions that are part of a Coulomb crystal in a cryogenic linear Paul trap. Specifically, we have monitored the decay of the |ν = 1, J = 1)(X) towards the |ν = 0, J = 0)(X) level in MgH+ by saturated laser excitation of the |ν = 0, J = 2)(X)-|ν = 1, J = 1)(X) transition followed by state selective resonance enhanced two-photon dissociation out of the |ν = 0, J=2)(X) level. The experimentally observed rate of 6.32(0.69) s(-1) is in excellent agreement with the theory value of 6.13(0.03) s(-1) (this Letter). The technique enables the determination of decay rates, and thus absorption strengths, with an accuracy at the few percent level.

Mast cells rescue implantation defects caused by c-kit deficiency.

Various physiologically relevant processes are regulated by the interaction of the receptor tyrosine kinase (c-Kit) and its ligand stem cell factor (SCF), with SCF known to be the most important growth factor for mast cells (MCs). In spite of their traditional role in allergic disorders and innate immunity, MCs have lately emerged as versatile modulators of a variety of physiologic and pathologic processes. Here we show that MCs are critical for pregnancy success. Uterine MCs presented a unique phenotype, accumulated during receptivity and expanded upon pregnancy establishment. Kit(W-sh/W-sh) mice, whose MC deficiency is based on restricted c-Kit gene expression, exhibited severely impaired implantation, which could be completely rescued by systemic or local transfer of wild-type bone marrow-derived MCs. Transferred wild-type MCs favored normal implantation, induced optimal spiral artery remodeling and promoted the expression of MC proteases, transforming growth factor-ß and connective tissue growth factor. MCs contributed to trophoblast survival, placentation and fetal growth through secretion of the glycan-binding protein galectin-1. Our data unveil unrecognized roles for MCs at the fetomaternal interface with critical implications in reproductive medicine.

Regional differences in susceptibility to hypoxic-ischemic injury in the preterm brain: exploring the spectrum from white matter loss to selective grey matter injury in a rat model.

Models of premature brain injury have largely focused on the white matter injury thought to underlie periventricular leukomalacia (PVL). However, with increased survival of very low birth weight infants, injury patterns involving grey matter are now recognized. We aimed to determine how grey matter lesions relate to hypoxic-ischemic- (HI) mediated white matter injury by modifying our rat model of PVL. Following HI, microglial infiltration, astrocytosis, and neuronal and axonal degeneration increased in a region-specific manner dependent on the severity of myelin loss in pericallosal white matter. The spectrum of injury ranged from mild, where diffuse white matter abnormalities were dominant and were associated with mild axonal injury and local microglial activation, to severe HI injury characterized by focal MBP loss, widespread neuronal degeneration, axonal damage, and gliosis throughout the neocortex, caudate putamen, and thalamus. In sum, selective regional white matter loss occurs in the preterm rat concomitantly with a clinically relevant spectrum of grey matter injury. These data demonstrate an interspecies similarity of brain injury patterns and further substantiates the reliable use of this model for the study of preterm brain injury.